Research focuses on the principles of protein structures and their associations, to relate protein structure and function. We center on the fundamental biophysical/biological processes, and in parallel, develop state of-the-art computational tools to enable their applications.Misfolded proteins malfunction. Amyloid formation is both intriguing and has extremely important practical implications. We study both peptide model systems and entire proteins with well documented experimental data. Computational studies can explore the details of the processes. For the model peptide systems our goals are to find the minimal seed size, theconformation of the protofibril and the mechanism of seed growth. The peptides are derived from myloidogenic proteins, and shown to form protofibrils. For the amyloidogenic proteins, we focus on the mechanisms through which native proteins undergo these conformational changes. Molecular dynamics can uniquely aid in supplying detailed information which can be used for drug design and in potential molecular probes for early detection. We focus on a number of molecules, particularly the Alzheimer's A-beta, the Islet amyloid polypeptide and polyglutamine. Our simulations have obtained results consistent with experiment. We present a theoretical investigation and experimental assays of the tendencies to form amyloid fibrils by a hexapeptide derivative of the human islet amyloid polypeptide, the NFGAIL (22-27) fragment and its mutants. The islet amyloid polypeptide is the major component of fibrillar deposits observed in more than 90% of patients with type II diabetes. Extensive experimental studies have indicated the ability of the polypeptide to form amyloid fibril assemblies that are toxic to pancreatic beta-cells. The 22-27 fragment of the polypeptide was shown to form toxic fibrillar structures that are morphologically similar to those formed by the full-length polypeptide. Thus, the peptide fragment presents a very good model system to study the basis of protein amyloid aggregation. We performed a complete alanine-scan of the 22-27 fragment and studied the capability of the wild-type and mutant peptides to form ordered fibers by ultrastructural and biophysical analysis. In parallel, we conducted a meticulous characterization of each sequence-complex at atomistic level by performing 9 independent explicit solvent molecular dynamics simulations for a total of 36 ns. We have been able to rationalize the experimental observations by means of molecular organization of the self-assembly and to describe the role of every residue in the amyloid fiber packing. We point to the critical importance of a coherent organization in the inter-sheet space and show that phenylalanine is the key in the maintenance of a regular organization pattern of this sequence. Its reduced conformational flexibility and ability to form oriented interactions with other aromatic residues, and non-specific hydrophobic interactions with aliphatic side chains, confer upon phenylalanine the ability to cement the macromolecular amyloid complex in all the amyloidogenic sequence variants of this peptide.The formation of fibril aggregates by long polyglutamine sequences is assumed to play a major role in neurodegenerative diseases such as Huntington. Understanding the molecular basis of the triggering of the abnormal folding of polyglutamine rich proteins is expected to be useful in preventing this group of pathologies. In this work, we present a molecular modeling study of peptides rich in glutamine, obtained through all atom explicit water molecular dynamics simulations. Starting from a rigid nanotube-like conformation, we have obtained a new conformational template that shares structural features of a tubular helix and a beta-helix conformational organization. Our new model can be described as a super-helical arrangement of flat beta-sheet segments coherently linked by planar turns or bends. We identify these bent regions as a new structural motif with a possible ordered organization within the amyloid fibrils, beyond that of the beta-sheet segments. In particular, we have further been able to discover that this type of conformational motif also exists in beta-helix proteins and in the proto fibril structure of the amyloidogenic peptide A-beta(1-40), pointing towards possible general modes of connecting long parallel beta-sheet segments that would allow the growth of partially ordered fibril structures.